Systemic Sclerosis And Related Fibrotic Diseases. Systemic sclerosis, more commonly referred to as scleroderma, is an uncommon autoimmune disorder of unknown etiology. The disease state is characterized by widespread vascular injury, perivascular and tissue accumulation of CD4+ T cells and monocytes, and excessive extracellular matrix deposition in skin and internal organs. More particularly, manifestations of systemic sclerosis include lowered IL-10 production by peripheral blood mononuclear cells and CD4.sup.+ CD26.sup.+ levels. Improvement of systemic sclerosis has been traditionally measured by application of the Modified Rodnan Skin Score and Modified Health Assessment Questionnaire.
Related disease states, including primary and secondary Raynaud's phenomena, and the severity of such states can be identified by these same characteristics and measurements.
While systemic sclerosis has been long and widely studied, for example, as reported by Garty, et al., 1991, Pediatrics 88:1161-1167 and Flick, et al., 1988, Pediatrics 82:107-111, no viable treatment has been shown to alter the disease's pathogenetic mechanisms. Rather, the diverse experimental treatments disclosed in the literature to date, including dexamethasone pulse therapy (Pai, et al., 1995, Int. J. Dermatol. 34(10):726-728), the administration of tissue plasminogen activator (Wilson, et al., 1995, J. Dermatol. 22(9):637-42) and the use of immunosuppressive agents, such as cyclophosphamide (Vallance, et al., 1995, Curr. Opin. Rheumatol. 7(3):174-182), have resulted in mixed findings. Various regimens to treat one or more compromised functions resulting from the onset of systemic sclerosis (e.g. Garty, et al., supra, disclosing the administration of D-penicillamine to benefit pulmonary function) have similarly failed to result in any significant improvements.
Oral Tolerance. Oral tolerance is the phenomenon by which the feeding of antigen results in specific unresponsiveness to the same antigen administered parenterally. Kagnoff, 1982, Ann.NY Acad. Sci. 392:248-265. The feeding of putative autoantigens has produced cellular tolerance and improvement or the prevention of disease in a number of animal models or autoimmune illnesses and diseases which are mediated by T-cells. See generally, Zhang, et al., 1991, Proc. Natl. Acad. Sci. (USA) 88:10252-10256; Nagler-Anderson, et al., 1986, Proc. Natl. Acad. Sci. (USA) 83:7443-7446; Lider, et al., 1989 J. Immunol. 142:748-752; Nussenblatt, et al., 1990, 142:1689-1695. In humans, it has been reported that the oral administration of myelin basic protein and type II chick collagen have been helpful in treating multiple sclerosis and rheumatoid arthritis, respectively. Weiner, et al., 1993, Science 259:1321-1324; Trentham, et al., 1993, Science 261:1727-1730.
Although systemic sclerosis and oral tolerance effects have been studied continuously since at least the early 1970's, prior to the instant invention, the phenomenon of oral tolerance had not been applied to the treatment of systemic sclerosis.